The clinical diagnosis of most neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD), currently relies on the analysis of symptoms and signs, limited laboratory tests, and more recently, brain imaging. The considerable overlap in the clinical presentation of these diseases, especially in their early course, increases the difficulty of distinguishing these diseases. In general, clinical diagnostic accuracy of various neurodegenerative diseases, as determined by pathological examination, falls between 50-85%, depending on the disease involved and the experience of the physician. Therefore, alternative approaches that are complementary and/or can provide greater selectivity and accuracy for disease diagnosis, especially at early clinical stage, are urgently needed. In the past few years, we have applied mass spectrometry based quantitative proteomics to study biomarkers related to neurodegenerative diseases. Such efforts have led to the identification of a group of protein biomarker candidates associated with AD and PD in cerebrospinal fluid (CSF), an ideal source for biomarker discovery in diseases related to the central nervous system (CNS). However, CSF is a less preferred diagnostic material compared to plasma or serum. Thus, in this proposal, we will apply a mass spectrometry based targeted quantitative proteomics approach to quantitatively detect and verify CSF biomarker candidates associated with AD and PD in human plasma. Successful completion of this project may lead to the development of clinician/patient-friendly sensitive assays that can assist with clinical diagnosis of AD and PD as well as monitor the progression of diseases or effects of current therapeutic reagents. In this study, we proposed to apply a mass spectrometry based targeted quantitative proteomics approach to quantitatively detect and verify CSF biomarkers associated with AD and PD in human plasma. We hope such effort will lead to or benefit the development of a clinicians-/patients-friendly sensitive assays that can assist with clinical diagnosis of AD and PD as well as monitoring the progression of diseases or effects of current therapeutic reagents. [unreadable] [unreadable] [unreadable]